PROJECT ABSTRACT Adolescents and young adults account for over one-third of all new global infections of HIV, representing a key population for prevention efforts. In sub-Saharan Africa, adolescent girls and young women (15-24) are more than twice as likely to become infected with HIV compared to their male counterparts and contribute nearly 25% of all new HIV infections in the region. Antiretroviral pre-exposure prophylaxis, or PrEP, has been found in clinical trials to be an efficacious biomedical HIV prevention strategy that holds enormous potential to reduce HIV acquisition in key populations globally. Among young African women, however, a range of adherence outcomes have been observed, with low adherence compromising PrEP efficacy in several trails. Further, adolescents under 18 years of age remain inadequately represented in PrEP research, posing a significant challenge for understanding how to deliver PrEP to young people with a focus on maximizing adherence. Research is needed to identify specific considerations relevant to the implementation of PrEP among adolescent girls and young women in generalized HIV epidemic settings. The objective of this study is to examine how disclosure of PrEP use and depression impact continuation of and adherence to daily oral PrEP among adolescent girls and young women in Eastern and Southern Africa. The specific aims of this research are to: (1) examine the association between disclosure of PrEP use to parents, partners, and peers and PrEP continuation and adherence; and (2) determine if depression is associated with PrEP continuation and adherence. This study will utilize longitudinal cohort data from EMPOWER, a multi-site prospective PrEP implementation study conducted among young women at substantial risk for HIV infection in Johannesburg, South Africa and Mwanza, Tanzania. A sample of 418 adolescent girls and young women (16-24 years of age) from the EMPOWER cohort who initiated daily oral PrEP will be included in this investigation. Participants were followed quarterly for up to 15 months. Adherence to PrEP, the primary study outcome, will be measured retrospectively using drug levels in dried blood spot samples for a biologic assessment of PrEP use. This investigation can help inform PrEP implementation strategies among adolescent girls and young women by providing insight into the social and psychological dynamics that facilitate adherence. To support the successful execution of this research project and promote the applicant?s growth into an independent investigator, additional training during the fellowship period will be sought to enhance the applicant?s collaborative research network, quantitative analysis skills, and interdisciplinary subject matter knowledge. Together, this proposed research and training plan will lay the foundation for the applicant?s future career as an independently funded epidemiologist focused on global health and HIV prevention research.